title: The effect of in vivo T cell depletion with alemtuzumab on reduced-intensity allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia.
abstract: Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation is increasingly considered for patients with chronic lymphocytic leukemia (CLL). To investigate the impact of in vivo T cell depletion with alemtuzumab on the incidence of graft-versus-host disease (GVHD), nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), we retrospectively analyzed the outcomes of 62 consecutive CLL patients conditioned with fludarabine and melphalan at 4 institutions. For GVHD prophylaxis, 41 patients (cohort 1) received alemtuzumab and cyclosporin; and 21 patients (cohort 2) received cyclosporin plus methotrexate or mycophenolate. Donors were 50 siblings and 12 unrelated volunteers. Twenty-two (36%) patients received donor lymphocyte infusions (DLI), 20 (49%) from cohort 1 and 2 (10%) from cohort 2 (P=.002). Grade III-IV acute GVHD (aGVHD) was observed in 20% and 38% of patients from cohorts 1 and 2, respectively (P=.14). Extensive chronic GVHD (cGVHD) was observed in 10% and 48% of patients from cohorts 1 and 2, respectively (P=.03). There was a trend toward a higher viral infection rate in cohort 1 compared to cohort 2 (68% versus 43%, P=.062), but the incidence of cytomegalovirus (CMV) reactivation was not significantly different. The 3-year OS, PFS, NRM, and relapse rates were 65%, 39%, 28%, and 32%, respectively, for cohort 1; and 57%, 47%, 34%, and 20%, respectively, for cohort 2 (P=.629, P=.361, P=.735, and P=0.112, respectively). In conclusion, both methods of GVHD prophylaxis were equivalent in terms of survival. The administration of alemtuzumab led to reduced cGVHD, possibly improving quality of life.
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. jdelgadog@santpau.cat
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.forename: Srinivas
authors.initials: S
authors.lastname: Pillai
authors.forename: Reuben
authors.initials: R
authors.lastname: Benjamin
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: Amit
authors.initials: A
authors.lastname: Nathwani
authors.forename: Richard
authors.initials: R
authors.lastname: Lovell
authors.forename: Kirsty
authors.initials: K
authors.lastname: Thomson
authors.forename: Jose A
authors.initials: JA
authors.lastname: Perez-Simon
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kottaridis
authors.forename: Lourdes
authors.initials: L
authors.lastname: Vazquez
authors.forename: Karl
authors.initials: K
authors.lastname: Peggs
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections; D018572:Disease-Free Survival; D046148:Donor Selection; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000628:therapy*; D019520:Living Donors; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D013601:T-Lymphocytes; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D016572:Cyclosporine